0000000000180935
AUTHOR
M. Molero-monfort
Micellar liquid chromatography for prediction of drug transport.
Abstract The vast majority of well absorbed drugs are transported passively across the cell membranes. Physicochemical descriptors of drug molecules that are believed to influence transcellular transport are routinely used to predict drug absorption by means of complex mathematical models. In this paper, a new in vitro method, based on the retention data in micellar liquid chromatography (MLC), is validated for the prediction of passive drug absorption. The retention of a heterogeneous drugs set in MLC using Brij 35 as surfactant in the mobile phase is compared with the retention data reported in literature obtained in red cell membrane lipid liposomes, human red cell membranes vesicles (ve…
Biopartitioning micellar chromatography: an in vitro technique for predicting human drug absorption.
The main oral drug absorption barriers are fluid cell membranes and generally drugs are absorbed by a passive diffusion mechanism. Biopartitioning micellar chromatography (BMC) is a mode of micellar liquid chromatography that uses micellar mobile phases of Brij35 under adequate experimental conditions and can be useful to mimic the drug partitioning process in biological systems. In this paper the usefulness of BMC for predicting oral drug absorption in humans is demonstrated. A hyperbolic model has been obtained using the retention data of a heterogeneous set of 74 compounds, which shows predictive ability for drugs absorbed by passive diffusion. The model obtained in BMC is compared with …
Development of predictive retention-activity relationship models of antipsychotic drugs by micellar liquid chromatography
The predictive and interpretative capability of quantitative chromatographic retention-biological activity models is supported by the fact that in adequate experimental conditions the solute partitioning into the chromatographic system can emulate the solute partitioning into lipid bilayers of biological membranes, which is the basis of drug and metabolite uptake, passive transport across membranes and bioaocumulation. The use of micellar solutions of Brij35 as mobile phases in reversed liquid chromatography has proven to be valid in predicting some biological activities of different kinds of drugs. In this paper, the correlations between the logarithm of capacity factors and pharmacokineti…
Development of Predictive Retention-Activity Relationship Models of Barbiturates by Micellar Liquid Chromatography
The need to get a tool for biological parameters estimation of new compounds for clinical applications, supports the postulation of predictive models as an alternative to conventional classical assays being no necessary the use of experimentation in animals. Our main aim in this work is to determine correlations between the logarithm of capacity factors and preclinical pharmacology and therapeutic efficacy parameters of barbiturates. The predictive and interpretative capability of quantitative chromatographic retention-biological activity models is supported by the fact that in adequate experimental conditions the solute partitioning into chromatographic system can emulate the solute partit…
Development of predictive retention-activity models of butyrophenones by biopartitioning micellar chromatography
The predictive and interpretative capability of quantitative chromatographic retention-biological activity models is supported by the fact that in adequate experimental conditions the solute partitioning into the chromatographic system can emulate the solute partitioning into lipid bilayers of biological membranes, which is the basis of drug and metabolite uptake, passive transport across membranes and bioaccumulation. The use of retention data obtained in biopartitioning micellar chromatography (BMC) has been demonstrated to be helpful in describing the biological behaviour of different kinds of drugs. In this chromatographic system, polioxyethylene 23 lauryl ether Brij35 micellar mobile p…
Potential of biopartitioning micellar chromatography as an in vitro technique for predicting drug penetration across the blood–brain barrier
The blood-brain barrier (BBB) is considered to be the main barrier to drug transport into the central nervous system (CNS). The BBB restricts the passive diffusion of many drugs from blood to brain. The ease with which any particular drug diffuses across the BBB is determined largely by the molecular features of drugs, and it is therefore possible to predict the BBB permeability of a drug from its molecular structure. Biopartitioning micellar chromatography (BMC), a mode of micellar liquid chromatography that uses micellar mobile phases of Brij35 in adequate experimental conditions, can be useful in mimicking the drug partitioning process into biological systems. Retention in BMC depends on…
Rapid in vitro test to predict ocular tissue permeability based on biopartitioning micellar chromatography.
The drug permeability prediction across the ocular tissues is important in the development of new drugs and drug delivery strategies. Physicochemical characteristics of drugs, mainly acid-base character, hydrophobicity and the molecular size determine both their transport across the eye tissue barriers and their retention in biopartitioning micellar chromatography (BMC). An in vitro model able to describe and predict the whole cornea drug permeability is proposed. The model uses the retention of drugs in BMC and molecular weight (MW) as predictive variables. The relationships between drug retention data in BMC and their bibliographic permeability values in stroma, epithelium-plus-stroma and…
Retention-activity relationship studies of benzodiazepines by micellar liquid chromatography
Solute partitioning into lipid bilayers of biological membranes is the basis for drug and metabolite uptake, passive transport across membranes and bioaccumulation. In order to emulate in vitro the partitioning process in the biomembranes, different approaches have been proposed. The use of micellar solutions as mobile phases in reversed-phase liquid chromatography (micellar liquid chromatography, MLC) has proven to be valid in the prediction of the biological activities of local anesthetics, catecholamines and barbiturates. In this paper we focus our attention on benzodiazepines. The retention of benzodiazepines using different concentrations of Brij35 as micellar mobile phase in modified …